By David N. Leff
Say your adolescent child enjoys an aggressive lifestyle, and is competing in this year's Junior Olympic Games for a medal in the skateboarding or roller-blading event. He or she risks a truly abrading experience, but if the scrape doesn't penetrate too deeply, the excoriated epidermis can call in specialized cells that will allow for skin repair.
Those standby cells lie densest in the 100,000 to 150,000 hair follicles that pave the adult human scalp, but they also deploy wherever in the body hair grows. The few hairless regions occur on the palms and soles of hands and feet, plus limited areas of male and female external genitalia.
Deeper than superficial abrasions are the debriding ravages of severe burn injury, which may obliterate large areas of epidermis altogether. Here, too - according to recently reported research - the hair follicles, besides their main gig of growing hair, can rescue and restore destroyed epidermis.
That announcement occurs in the current issue of Cell, dated Aug. 18, 2000, under the title: "Involvement of follicular stem cells in forming not only the follicle but also the epidermis." Its co-senior authors are skin biologists Robert Lavker at the University of Pennsylvania in Philadelphia, and Tung-Tien Sun at New York University.
"Our finding suggests," Lavker told BioWorld Today, "that the hair follicle is not merely a cosmetic entity. It's not there just to make us look good or - depending on your image - look bad. We show that the hair follicle really serves a much more important function - to help maintain the epidermis in times of need.
"It had long been appreciated," he continued, "that if one were to lose a great deal of one's epidermis - the outermost layer of the skin - when this layer reformed, it would occur in little islands of skin over the denuded part. These often centered around the opening of the hair follicle, which gave the suggestion that that follicle may participate in re-epithelializing the epidermis."
In the 1990s, he and Sun reported that the stem cells - which are the grandmother cells of any self-renewing tissue - were localized in a portion of the hair follicle called the bulge. They postulated that if these were truly stem cells, their cellular progeny - the daughter cells - would actually replenish the epidermis.
"Our paper in Cell this past Friday," Lavker pointed out, "shows rather conclusively that the daughter cells of the stem cells reside in the upper part of the follicle, and that they can traffic into the epidermis in times when there is a great need for more cells - as in the newborn, and in response to small wounds. This really showed for the first time where in the hair follicle the cells responsible for re-epithelialization occurred.
"Just as importantly," he went on, "it indicated that the stem cells in the hair follicle's bulge region could indeed be bipotent, in that their daughters could give rise to cells that would travel downward and make a hair shaft - which is morphologically and chemically quite distinct from an epidermis. Likewise, with the appropriate signals, these bulge cells would give rise to cells that could migrate upward and make an epidermis."
It's All In The Bulge
In humans, the hair follicle rises from a couple of millimeters below skin surface in a bulb where new hair shafts are born. Closer to the surface, follicles put out their sebaceous gland, which, Lavker explained, "contains the waxy oil, bacteria and other cells responsible for the adolescent vexations and torture of acne."
Between this gland above and the bulb below, hair follicles form from one side of the gently bulging protuberance that houses the follicular epithelial stem cells, as well as - in Lavker's hypothesis - the epidermal stem cells. "That outpouching," he pointed out, "about 300 microns in length, is the insertion site of the erector pili muscle - which, when it contracts, makes your hair stand on end. It anchors itself right into the follicle."
Describing the origin and fate of hair follicles, Lavker observed: "You're pretty much born with whole clusters of them. They undergo periods of growth - anagen - when the follicular bulb at the bottom is growing the cells destined to become the hair shaft. But before they differentiate into the various components of that shaft, these basal cells are known as matrix keratinocytes. They are the most rapidly proliferating cells in the body.
"So that bulb is a powerhouse of cell division. And the division rate at the time the hair is growing is unparalleled. We believe that these daughter cells run out of gas," Lavker went on. "They have a finite number of divisions - that's what separates a daughter cell from a stem cell. Theoretically, a stem cell will divide for the lifetime of the organism. These cells divide, until they've run out of their proliferative potential, which can be prodigious, but still is finite. So at that point the hair follicle stops making cells programmed to make a hair shaft.
"Instead it undergoes a period of destruction - catagen - which is really apoptosis. One-third of that follicle becomes destroyed. But not its bulge. You don't want your stem cells to be destroyed.
"And then," Lavker recounted, "the follicle sits in a resting stage - telogen - for a while. In male pattern baldness, it seems to be resting forever. But - hopefully- most of your follicles, after a period of time, get some kind of a cue, or cues: Take these sleeping stem cells and have them reawaken and start the hair follicle process growing again."
Prime Payoff: Refueling Wasted Psoriatic Cells
Turning to potential applications of his bulge discovery, Lavker began with two disclaimers: "Our current finding won't do much for hair growth in the foreseeable future, nor for treating skin cancer, because dermatologists can already cure basal cell carcinoma efficiently. Gene therapy is a potential, but wound healing is key.
"Obviously," he observed, "the upper part of the follicle plays a central role in wound repair. If you have wounds, then your follicular epithelium cells can mimic and make an epidermis."
He added one more immediate idea: "The only thing I would suggest now is that in hyperproliferative skin diseases, such as psoriasis, there's a need for the epidermis to have a constant supply of proliferatiting cells - because that's the nature of the disease. We propose," Lavker concluded, "that the hair follicle might be a reservoir and a source of some of these cells - involved in fueling psoriatic epidermis."